Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.     

Dithiocarbamate-induced biliary platinum excretion and the control of cis-platinum nephrotoxicity

Treatment with any one of six different dithiocarbamates subsequent to the administration of cis-platinum (CDDP) is shown to promote the biliary excretion of platinum. The administration of the most effective of these compounds, sodium diethyldithiocarbamate (DDTC) at 1.57 mmol/kg, led to a 30-fold increase in the biliary excretion of platinum. For the other dithiocarbamates investigated, a similar dosage led to increases ranging from approximately 5-fold for sodium iminodiacetic acid dithiocarbamate, to 26-fold for sodium sarcosine dithiocarbamate. The presence of alkyl groups on the nitrogen of the dithiocarbamate increased the effectiveness of the compounds. There is no increase in the platinum levels of the brain when DDTC is used in this manner. A histopathological evaluation of the kidneys of rats given 15 mg CDDP/kg in 6.3% saline with and without the use of dithiocarbamates for renal protection shows significant additional protection due to the use of the dithiocarbamates. Dithiocarbamates given at an appropriate dosing schedule can lead to a significant reduction in the renal damage which is revealed by microphotographs. It is suggested that part of the renal protection obtained by the use of dithiocarbamates may be due to this shift of platinum excretion to the bile which obviates additional renal exposure to platinum. It was also found that the simultaneous injection of a dithiocarbamate with the cis-platinum has no obvious effect on the anti-cancer action of cis-platinum against the Walker 256 carcinosarcoma in rats.     

Catecholaminergic and opioidergic mechanisms involved in the hypotensive response of pindolol

The present study evaluated the involvement of opioidergic and catecholaminergic mechanisms in the hypotensive action of pindolol. Pindolol (1 mg/kg i.a.) was administered to unanesthetized spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats instrumented for direct arterial pressure monitoring. Peripheral administration of pindolol produced a significant decrease in blood pressure in both SHR and WKY rats with SHR animals having a greater response. Heart rate was reduced in SHR; however, a tachycardia was observed in WKY rats. Pretreatment with naloxone (100 micrograms/kg i.a.) 10 min prior to pindolol administration prevented the hypotensive response. Similar pretreatment with yohimbine, an alpha 2-receptor antagonist, also prevented the pindolol-induced hypotensive response in both SHR and WKY rats. Neither naloxone nor yohimbine alone significantly affected blood pressure or heart rate. These results suggest that opioidergic and catecholaminergic mechanisms are involved in the hypotensive action of pindolol.     

Parapubic hernia: case report and review of the literature

Parapubic hernia is considered rare, with 18 hernias described in five articles published since 1971. The hernia results from iatrogenically or traumatically detached rectus abdominis muscles at the pubic bone and presents a therapeutic challenge because there is no strong aponeurotic anchoring structure in the defect's caudal aspect. We describe a patient with a large parapubic hernia repaired by a combined preperitoneal and onlay prosthetic method. This report adds another dimension to the prosthetic repair options in parapubic hernias and illustrates the effectiveness of the tension-free repair principle in their definitive management. Electronic Publication     

Urinary calculi in children in Western Australia: 1972-86

Records of all children presenting with urinary calculi in the period 1972-86 were reviewed in order to detail clinical features, laboratory and radiographic findings and treatment. Of a total of 85 children, 59 were Aboriginal and 26 were Caucasian. The features of urolithiasis differed between these groups. In the Aboriginal patients, calculi consisted mainly of uric acid and urates. Important clinical characteristics of this group included a young age at presentation (median = 2.1 years) and frequent presentation with failure to thrive. Calculi were commonly located in the upper urinary tract and most required surgical removal. Documented sequelae included renal scarring and hypertension. Caucasian children presented at a later age (median = 10.5 years), frequently with abdominal pain, and most calculi were associated with an underlying urological or metabolic abnormality.     

A computational model for the overall pattern of ocular dominance.

In layer IV of the primary visual cortex, in both the macaque monkey and the cat, geniculocortical terminals representing the two eyes are segregated into alternating zones known as ocular dominance bands. Viewed tangentially, in the monkey these bands take the form of a series of branching parallel stripes that run roughly perpendicular to the border of striate cortex. In the cat, the overall ocular dominance pattern consists of irregularly branching, beaded bands that exhibit no predominant orientation. If the striking differences in the appearance of these two patterns reflect important differences in the basic rules governing cortical ocular dominance, then this poses a problem for attempts to formulate general principles of visual cortical organization. However, it has been suggested that the differences in the appearance of the ocular dominance patterns in these two species could result simply from known differences in the boundary conditions of their geniculocortical pathways. This article describes the formulation and testing of a single computational model that accurately predicts the quite dissimilar ocular dominance patterns in cats and monkeys. This model also generalizes to predict the different ocular dominance patterns observed in young and old three-eyed frogs, supporting the notion that the overall pattern of ocular dominance is governed by a common set of rules. The significance of these results is discussed in terms of previous models, which have focused largely on local processes underlying the development of ocular dominance segregation. Although the present model is not a developmental one, it does shed some light on potential mechanisms for establishing retinotopy in striate cortex and on possible developmental relationships between the geniculostriate pathway and intrinsic modularity of the striate cortex.     

Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.

Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.     

Central corticotropin releasing factor reduces natural cytotoxicity. Time course of action

Corticotropin-releasing factor (CRF) administered intracerebroventricularly produced both a rapid, greater than 50% reduction in splenic natural killer (NK) cytotoxicity and a prolonged elevation in plasma corticosterone levels. In the first 60 minutes following CRF, fivefold increases in corticosterone levels were associated with the suppression of NK activity. However, NK activity returned to control levels at later time points even though elevated plasma corticosterone levels persisted. These data augment the findings that central CRF reduces natural cytotoxicity and establish a time course for the effect in acutely treated rats.     

Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy.

OBJECTIVE. Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. MATERIALS AND METHODS. Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. RESULTS. Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. CONCLUSION. Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.